For healthcare professionals. Compounded preparations are dispensed on a doctor’s prescription.
Short answer: Tretinoin cream has been tested in vehicle-controlled trials of photodamaged facial skin. The strength and base a patient needs are the prescriber’s decision, and the trials describe only the formulations they tested. A compounded tretinoin preparation is made only for one named patient, on a doctor’s prescription.
Why photoageing is a prescribing question
A 2025 network meta-analysis describes chronic ultraviolet exposure as “the primary cause of skin photoaging, leading to wrinkles, pigmentation changes, and loss of dermal elasticity” (Lin et al., 2025; PMID 40707570). The 1991 multicentre study reported changes in fine wrinkling, mottled hyperpigmentation, roughness and laxity in photodamaged facial skin (Weinstein et al., 1991; PMID 2024983).
For a prescriber, the practical question is less whether tretinoin has been studied than whether the strength and base a named patient needs can be matched to what those trials used. The trials describe the study formulations they tested, not any compounded preparation. A prescriber who needs a strength or base outside the strengths and bases tested in the cited trials is facing a formulation question, and the answer belongs in the prescription.
Photoageing shows up in several signs at once. Leyden et al. (1989) reported changes in fine wrinkling, coarse wrinkling, sallowness, looseness and hyperpigmentation (PMID 2674225), and Weinstein et al. (1991) reported changes in fine wrinkling, mottled hyperpigmentation, roughness and laxity (PMID 2024983). A prescriber reviewing a named patient can record the same signs at baseline and at each review, so that the change is documented rather than estimated from memory.
The active and what the trials measured
The closest the cited records come to a mechanism is histological. The 1991 multicentre study reported “increased epidermal thickness, decreased melanin content, and stratum corneum compaction”, which its authors described as independent evidence supporting clinical improvement (Weinstein et al., 1991; PMID 2024983). The cited records describe these tissue changes, not a molecular pathway.
Two of the trials below used 0.05% tretinoin. The multicentre study also tested 0.01%, in an emollient cream base. The strength a prescriber chooses for a named patient is a separate decision from these study conditions, and should be stated in the prescription.
What the trials show
| Study | Design and population | Outcome as reported | PMID |
|---|---|---|---|
| Leyden et al., 1989 | Randomised, double-blind, vehicle-controlled, 6-month study of 0.05% cream once daily in photodamaged facial skin | Fine wrinkling, coarse wrinkling, sallowness, looseness and hyperpigmentation significantly improved with tretinoin therapy | 2674225 |
| Weinstein et al., 1991 | Randomised, double-blind, vehicle-controlled multicentre study; 251 subjects with mild to moderate photodamaged facial skin | 79% of subjects on 0.05% for 24 weeks showed overall improvement, compared with 48% of vehicle-treated controls | 2024983 |
| Lin et al., 2025 | Systematic review and network meta-analysis of 23 randomised trials; 3,905 participants | Isotretinoin, retinol and tretinoin significantly improved fine wrinkles, with isotretinoin ranked highest | 40707570 |
Leyden et al. (1989) reported that “Fine wrinkling, coarse wrinkling, sallowness, looseness, and hyperpigmentation were significantly improved with tretinoin therapy” (PMID 2674225). Weinstein et al. (1991) reported that 79% of subjects who received 0.05% tretinoin for 24 weeks showed overall improvement, compared with 48% of vehicle-treated controls (PMID 2024983).
Both single trials were vehicle-controlled, so each compares tretinoin with a vehicle base rather than with another active (PMID 2674225, PMID 2024983).
Lin et al. (2025) pooled 23 randomised trials with 3,905 participants. Their Bayesian network meta-analysis reported that “isotretinoin, retinol, and tretinoin significantly improved fine wrinkles, with isotretinoin ranked highest” (PMID 40707570). The result is a comparison across agents, and it does not single out tretinoin in a head-to-head trial.
Strengths and schedules in the cited trials
The strengths and schedules below are those each study reports for the formulation it tested.
| Study | Strength and vehicle | Schedule or duration | PMID |
|---|---|---|---|
| Leyden et al., 1989 | 0.05% tretinoin cream | Once daily, 6 months | 2674225 |
| Weinstein et al., 1991 | 0.05% and 0.01% tretinoin emollient cream | 0.05% for 24 weeks | 2024983 |
The trials tested these strengths and schedules. They do not set a dose for any individual patient. A prescriber who chooses a strength below that range, or a base other than the emollient cream used in the multicentre study, is moving away from the trial conditions, and should record that choice in the prescription and in the patient’s notes.
Where compounding fits
When a prescriber’s chosen strength or base falls outside those tested in the cited trials, compounding is the route. The strength and base are the prescriber’s decision and should be stated on the prescription, so that the preparation matches the specification the prescriber set.
Safety and tolerability
Weinstein et al. (1991) reported that “Side effects of erythema, peeling, and stinging were usually mild and well tolerated” (PMID 2024983). The 2025 network meta-analysis reported that “Safety analysis indicated tretinoin had the most favorable profile” among the agents it compared (Lin et al., 2025; PMID 40707570).
The cited records do not address pregnancy, so pregnancy status and other contraindications are for the prescriber to check before any prescription. A prescriber can set out in the review plan how erythema, peeling and stinging would be assessed in the named patient, since those are the effects the 1991 study recorded.
Checklist before prescribing
- Record the indication in the patient’s own clinical terms, and whether a tretinoin product has already been tried.
- Record pregnancy status and any plans to conceive, since the cited records do not address this.
- Note the other topical actives the patient uses, including any pigmentation treatment, so the full regimen sits on one page.
- Set the strength and base in the prescription, referring to the strengths tested in the tables above.
- Set the review interval and the points the prescriber will reassess, including tolerability.
Limits of the evidence and what this means for prescribing
The network meta-analysis lists its own limitations: “limited racial diversity, potential commercial bias, and variability in dermatological assessments” (Lin et al., 2025; PMID 40707570). For a patient whose skin type is outside the populations those trials describe, the prescriber should weigh that limited racial diversity against the patient in front of them.
The two single trials are older studies, of six months (Leyden et al., 1989; PMID 2674225) and 24 weeks (Weinstein et al., 1991; PMID 2024983). The 1989 study tested 0.05% only, and the 1991 study tested 0.05% and 0.01%. Neither set out a regimen for longer use, so the duration after 24 weeks is the prescriber’s decision. The prescriber also sets the strength, base and review interval.
Readers comparing photoageing with pigmentation may also read our guides to compounded melasma and pigmentation topicals in Malaysia, compounded brightening creams for pigmentation and prescription tranexamic acid for melasma.
Reviewed by Vitthia Rama Murti, RPh (RPh 15632).
How to prescribe
A compounded tretinoin preparation is made only on the prescription of a registered doctor, for one named patient, under Good Compounding Practice (GCP). The laboratory standards are set out on our GCP laboratory page.
The prescription should state the active (tretinoin), the strength, the form (cream), the quantity and the directions for use, including the area of application and any other active the prescriber has chosen. Cream may be prepared in an ordinary or liposomal form to the prescriber’s specification.
Send the signed prescription through our contact page. Vitthia Rama Murti, RPh (RPh 15632), can be contacted through the same page, and our pharmacists team page sets out the team.
Frequently asked questions
Can a compounded tretinoin cream be supplied without a prescription?
No. A compounded tretinoin cream is prepared for one named patient on a registered doctor’s prescription, under Good Compounding Practice (GCP). The prescription should state the active, strength, form, quantity and directions, so the preparation matches the prescriber’s specification.
What strengths did the photoageing trials use?
The cited trials used 0.05% tretinoin, and one multicentre study also tested 0.01% in an emollient cream (PMID 2024983). Leyden et al. (1989) studied 0.05% cream once daily for six months (PMID 2674225). Weinstein et al. (1991) reported that 79% of subjects on 0.05% for 24 weeks showed overall improvement, compared with 48% of vehicle-treated controls (PMID 2024983).
Does the evidence support tretinoin for fine wrinkles?
A 2025 network meta-analysis of 23 randomised trials with 3,905 participants reported that isotretinoin, retinol and tretinoin significantly improved fine wrinkles, with isotretinoin ranked highest (PMID 40707570). The same analysis lists limited racial diversity among its limitations.
What side effects did the trials report?
Weinstein et al. (1991) reported that side effects of erythema, peeling and stinging were usually mild and well tolerated (PMID 2024983). The cited records do not address pregnancy, so pregnancy status is for the prescriber to check before any prescription.